DNA… Nurture Your Nature – Session Eight

Your Most Valuable Asset – Your Brain!

Keep It Sharp for Decades.

DNA+Environment+Triggers+Chance = Future Brain Health

Stay Sharp by Modifying the Expression of APOE, TREM2, ABCA7 and CD33 Genes

– Bruce Alan Kehr, M.D.

Reader, what would you do if I told you that you didn’t need coffee to clear your mind every morning—that you could reach that same cognitive uptick through changing your diet and your lifestyle? What if you could even slow cognitive decline over time, keeping your brain sharp well into the future? That’s what this blog is about today: Your brain and mental cognition.

In our wellness-saturated world, you probably have multiple ways of keeping your brain alert and your body healthy. Maybe you do yoga, or limit your imbibing of alcoholic beverages to the weekend. Perhaps you take supplements recommended to you by your favorite lifestyle blogger. These are all great habits that MAY act as non-specific (“non-targeted”) prophylaxis to aging concerns (we know well at this point that exercising has long-lasting positive effects that can sustain us well into our old age.) But sometimes, the wellness game can feel like we’re trying to hit a target with a blindfold on. We know the general goods—heart health, keep our minds healthy, keep our bones sturdy—but what if there was a way for us to discover our body’s secret vulnerabilities, and pinpoint our personalized health and wellness regimen accordingly?

WE NOW HAVE THE TECHNOLOGY TO TAKE OFF THAT BLINDFOLD AND HIT THE BULLSEYE!

Suddenly, you’re not taking fish oils just because you heard they might help with brain aging—you’re taking them because you know you have a gene with a particular mutation that leaves you more susceptible to Alzheimer’s, and taking fish oils consistently may just change the damaging expression of that gene, to upregulate or downregulate its expression—to transform the harmful effects of that mutation into an average person’s genetic risk—or even to promote a resilient brain.  That’s powerful knowledge we could bring into our lives—and it’s not just a fantasy. What goes on inside our bodies, and within the cells that make us who we are, can feel like a mystery, but genetic testing offers us a precise view of who we are at the level of our DNA—how it expresses itself to create the structure and function of each and every cell within us—and we are gaining more and more tools over time to pair that precise view with precise treatments and recommendations so you can give yourself the best chance at a long, healthy, and mentally present life.

For the next six weeks, we’re going to dive one-by-one into the six domains of our body, as elucidated by Genomind’s Mindful DNA genetic test—cognition and mental acuity, stress and emotional wellbeing, cardiometabolic, inflammation, gastrointestinal and immune, and sleep. Following up our in-depth look into Alzheimer’s disease from the last couple weeks, we’re starting with the domain called “Cognition and Mental Acuity.” Each week, we’ll look at a new domain as a whole and examine how it relates and interconnects with the other five domains responsible for our overall wellness destinies. We’ll also look at a few examples of genes within each domain, and how you might tweak your lifestyle (including supplements, diet, and other interventions) to upregulate or downregulate some of your genes, using epigenetic modifiers, into a lower-risk-of-chronic-disease expression.

So, reader, if you want a healthier brain—to feel better and function more effectively in your life—and especially if you want to prevent or postpone mental decline… this week’s blog is for you. Let’s go!

Cognition and Mental Acuity: How Does This System Work?

Remember when I asked you at the beginning of this series to consider where, specifically, your feeling of tiredness or achiness—or stress or anger—really lived within your body? As I mentioned in a prior post, the answer is those feelings don’t really live in any one place: they’re decentralized, originating from and affecting multiple parts of our body at once. This is how our genes work as well. While our genes are hyper-focused in terms of their purpose, their variations—both those we’re born with and those changed through spontaneous mutations—can lead to different outcomes or consequences in different parts of our bodies.  Genes classified as having an impact on our cognition and mental acuity are those genes whose purposes lie generally in brain-related functioning, whether that gene is responsible for your higher risk of a migraine—or your higher risk of depression. Yes, those genes have impacts on other systems as well: but you could say their central impact is brain-related.

Now if you’ve learned anything from this DNA series, I hope it’s that science tells us our bodies are a two-way street, so to speak: our genes affect our outcomes—but our external lifestyle choices affect the functioning of many of our genes. It’s a constant cycle of adaptation: lifestyle influencing genetic expression, genes influencing lifestyle-related health outcomes. So while it’s important for us to discuss how the Cognition and Mental Acuity genes impact our mental wellness, it’s just as important to discuss how our lifestyle choices can impact how these genes determine the structure and function (the health or disease) of our cells. That’s what the Mindful DNA test is all about, and that’s what we’ll be focusing on in these upcoming posts.

So, the genes that are primarily responsible for keeping our basic brain functioning healthy have an impact on our moods and mental clarity—and the rate of our eventual cognitive decline. And we can nurture our Cognition and Mental Acuity genes by avoiding or practicing certain lifestyle choices, regardless of which genes we’ve inherited. Obesity and a habit of smoking are two key lifestyle measures that can directly impact these genes for the worse. Similarly, physical activity and cognitive training interventions can impact them for the better. But genetic testing lets us take a deeper look into more personalized and targeted habits to improve our memory and executive functions now and into the future.

Key Genes That Affect our Mental Outcomes – TREM2, APOE, ABCA7, CD33—and What You Can Do about Them

Several of the genes listed under the Cognition and Mental Acuity domain are ones you’ve heard of before in our prior series, “DNA: I Am Who I Am… or Am I?” Centering on Genomind’s Genecept Assay, that series focused specifically on genes that may lead us to a predisposition for mental illness, and focused on precision treatment options related to specific genetic mutations or variations. Genes like BDNF, CACNA1C, ANK3 and COMT will all sound familiar to you—and they’re all found in this brain-related domain because of course they have a major impact on our cognitive health! Mindful DNA focuses on non-prescription changes to your lifestyle to modify your genetic expression, and while its recommendations address the genetic variations in these genes, in this brief summary I want to focus on genes that have a more hidden impact: genes that, if we don’t account for and modify their expression now, may alter our long-term future for the worse—specifically by putting us at risk for Alzheimer’s Disease. They include:

TREM2: As we learned in last week’s post, a rare variant in the TREM2 gene can lead to a heightened risk of developing Alzheimer’s Disease. This gene codes for a receptor on the surface of the brain’s “microglial cells”—a vital receptor that triggers a critically important process—one that is both anti-inflammatory and metabolizes (destroys) debris from cells that have died as well as destroying dangerous proteins that build up in the brain. The failure of this receptor to function normally – a “side-effect” of a TREM2 mutation—we now understand as a core component of Alzheimer’s progression. Abnormal protein build-up is one of the causes leading to the slow progression of Alzheimer’s in our brains—and if your TREM2 gene happens to have a mutation that leaves it less able to metabolize those proteins, it’s easy to see how your risk begins to increase. Now, all precision treatments of these mutations is ultimately between you and your own doctor—but if you know this TREM2 mutation is one you have, you might consider the benefit of ensuring a full eight hours of sleep a night, for starters. It’s during our sleep cycle that our glymphatic system—the system of flushing out those protein buildups in our brain—does its crucial work. And given that TREM2 is not the only gene dictating protein buildup, giving your body every opportunity to flush out proteins through other, more efficient genes or processes could fundamentally change the course of your future brain health.

APOE: Meta-analyses of numerous scientific studies has shown that those of us who possess a certain allele of the gene known as APOE (those who have inherited APOE4) are significantly more likely to develop Amyloid β plaques—the plaques that contribute to the development of Alzheimer’s Disease. Interestingly, studies have also found that DHA supplementation prior to the onset of Alzheimer’s may reduce the risk associated with the gene. DHA is a component of Omega 3. This is precision medicine in action—and all without a prescription medication.

ABCA7: Variants of this gene are similarly associated with dysregulated clearance of those Amyloid β plaques—and with the inflammation that ensues from that dysregulation. Mindful DNA specifically tests for the G allele variant, which is associated with an estimated 17-20% increased likelihood of developing Alzheimer’s. It’s also significantly associated with “sub-syndromal” predictors of Alzheimer’s, such as mild cognitive impairment. ABCA7 is involved in coding for processes that clear Amyloid β proteins and dead cell debris from our brains – to prevent the damaging effects of their accumulation. Epigenetic modifiers may include Mediterranean diet, melatonin, olive oil polyphenols, curcumin and others.

CD33: Variants of this gene determine a receptor on the microglial cells that is responsible for an “on-off” switch in the cells. If “turned on” the cells clear out amyloid and other bad debris, and if “turned off” it leads to oxidative stress and damaged neurons. Epigenetic modifiers here may include Vitamin D supplementation, and carotenoids.

Conclusion: Cognition and Your Future

Each of the genes outlined above is related to multiple other domains, including sleep and inflammation. Indeed, habitual lack of sleep is a key risk factor negatively affecting the expression of almost all of the genes found within the Cognition domain. Inflammation is a natural process, but when it becomes chronic—especially in the brain, as a consequence of the expression of one of these genes or many others—it can have disastrous implications.

These genes are just four of many examples of how your DNA may be putting you at risk for mental decline far earlier than you’d intend. But, that doesn’t mean that has to be your future fate. By taking a genetic test, you can assess for and implement health-improving life-saving  options now, rather than waiting for disaster to strike later in life.

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